Acetaldehyde-induced increase in paracellular permeability in Caco-2 cell monolayer

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Evidence indicates that endotoxin-mediated liver injury plays an important role in the pathogenesis of alcoholic liver disease. Elevated plasma endotoxin level in alcoholics is suggested to be caused by enteric bacterial overgrowth and/or increased intestinal permeability to endotoxin. In this study, the effect of ethanol and acetaldehyde on the paracellular permeability was evaluated in Caco-2 cell monolayers. Ethanol was administered into the incubation medium, whereas acetaldehyde was administered by exposing cell monolayers to vapor phase acetaldehyde, or by direct administration of an acetaldehyde generating system (AGS), ethanol + NAD+ + alcohol dehydrogenase. Paracellular permeability was assessed by measuring transepithelial electrical resistance (TER), sodium chloride dilution potential, and unidirectional flux of D-[2-3H]mannitol. Administration of ethanol up to 900 mM produced no significant effect on paracellular permeability. Vapor phase acetaldehyde, generated from 5 to 167 mM acetaldehyde solutions in neighboring wells, resulted in a time- and dose- dependent increase in acetaldehyde concentration (99 to 760 μM) in the buffer bathing cell monolayer. Acetaldehyde induced a reduction of TER and dilution potential, and an elevation of mannitol flux in a time and concentration-related manner, without affecting the ability of cells to exclude trypan blue. Removal of acetaldehyde after 1, 2, or 4 hr treatment and subsequent incubation in the absence of acetaldehyde resulted in a time- dependent reversal of TER to baseline values. Administration of AGS also reduced TER and dilution potential, associated with an increase in mannitol flux. This effect of AGS was prevented by 4-methylpyrazole, an alcohol dehydrogenase inhibitor. These results show that acetaldehyde, but not ethanol, reversibly increases the paracellular permeability of Caco-2 cell monolayer.

Original languageEnglish (US)
Pages (from-to)1724-1730
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Volume22
Issue number8
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

Fingerprint

Caco-2 Cells
Acetaldehyde
Monolayers
Permeability
Acoustic impedance
Electric Impedance
Ethanol
Mannitol
Endotoxins
Dilution
Alcohol Dehydrogenase
Fluxes
Liver
Vapors
Alcoholic Liver Diseases
Trypan Blue
Alcoholics
Sodium Chloride
Buffers

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Cite this

Acetaldehyde-induced increase in paracellular permeability in Caco-2 cell monolayer. / Rao, Radhakrishna.

In: Alcoholism: Clinical and Experimental Research, Vol. 22, No. 8, 01.01.1998, p. 1724-1730.

Research output: Contribution to journalArticle

@article{613deabc6c754901bf70f900b845e225,
title = "Acetaldehyde-induced increase in paracellular permeability in Caco-2 cell monolayer",
abstract = "Evidence indicates that endotoxin-mediated liver injury plays an important role in the pathogenesis of alcoholic liver disease. Elevated plasma endotoxin level in alcoholics is suggested to be caused by enteric bacterial overgrowth and/or increased intestinal permeability to endotoxin. In this study, the effect of ethanol and acetaldehyde on the paracellular permeability was evaluated in Caco-2 cell monolayers. Ethanol was administered into the incubation medium, whereas acetaldehyde was administered by exposing cell monolayers to vapor phase acetaldehyde, or by direct administration of an acetaldehyde generating system (AGS), ethanol + NAD+ + alcohol dehydrogenase. Paracellular permeability was assessed by measuring transepithelial electrical resistance (TER), sodium chloride dilution potential, and unidirectional flux of D-[2-3H]mannitol. Administration of ethanol up to 900 mM produced no significant effect on paracellular permeability. Vapor phase acetaldehyde, generated from 5 to 167 mM acetaldehyde solutions in neighboring wells, resulted in a time- and dose- dependent increase in acetaldehyde concentration (99 to 760 μM) in the buffer bathing cell monolayer. Acetaldehyde induced a reduction of TER and dilution potential, and an elevation of mannitol flux in a time and concentration-related manner, without affecting the ability of cells to exclude trypan blue. Removal of acetaldehyde after 1, 2, or 4 hr treatment and subsequent incubation in the absence of acetaldehyde resulted in a time- dependent reversal of TER to baseline values. Administration of AGS also reduced TER and dilution potential, associated with an increase in mannitol flux. This effect of AGS was prevented by 4-methylpyrazole, an alcohol dehydrogenase inhibitor. These results show that acetaldehyde, but not ethanol, reversibly increases the paracellular permeability of Caco-2 cell monolayer.",
author = "Radhakrishna Rao",
year = "1998",
month = "1",
day = "1",
doi = "10.1111/j.1530-0277.1998.tb03972.x",
language = "English (US)",
volume = "22",
pages = "1724--1730",
journal = "Alcoholism: Clinical and Experimental Research",
issn = "0145-6008",
publisher = "Wiley-Blackwell",
number = "8",

}

TY - JOUR

T1 - Acetaldehyde-induced increase in paracellular permeability in Caco-2 cell monolayer

AU - Rao, Radhakrishna

PY - 1998/1/1

Y1 - 1998/1/1

N2 - Evidence indicates that endotoxin-mediated liver injury plays an important role in the pathogenesis of alcoholic liver disease. Elevated plasma endotoxin level in alcoholics is suggested to be caused by enteric bacterial overgrowth and/or increased intestinal permeability to endotoxin. In this study, the effect of ethanol and acetaldehyde on the paracellular permeability was evaluated in Caco-2 cell monolayers. Ethanol was administered into the incubation medium, whereas acetaldehyde was administered by exposing cell monolayers to vapor phase acetaldehyde, or by direct administration of an acetaldehyde generating system (AGS), ethanol + NAD+ + alcohol dehydrogenase. Paracellular permeability was assessed by measuring transepithelial electrical resistance (TER), sodium chloride dilution potential, and unidirectional flux of D-[2-3H]mannitol. Administration of ethanol up to 900 mM produced no significant effect on paracellular permeability. Vapor phase acetaldehyde, generated from 5 to 167 mM acetaldehyde solutions in neighboring wells, resulted in a time- and dose- dependent increase in acetaldehyde concentration (99 to 760 μM) in the buffer bathing cell monolayer. Acetaldehyde induced a reduction of TER and dilution potential, and an elevation of mannitol flux in a time and concentration-related manner, without affecting the ability of cells to exclude trypan blue. Removal of acetaldehyde after 1, 2, or 4 hr treatment and subsequent incubation in the absence of acetaldehyde resulted in a time- dependent reversal of TER to baseline values. Administration of AGS also reduced TER and dilution potential, associated with an increase in mannitol flux. This effect of AGS was prevented by 4-methylpyrazole, an alcohol dehydrogenase inhibitor. These results show that acetaldehyde, but not ethanol, reversibly increases the paracellular permeability of Caco-2 cell monolayer.

AB - Evidence indicates that endotoxin-mediated liver injury plays an important role in the pathogenesis of alcoholic liver disease. Elevated plasma endotoxin level in alcoholics is suggested to be caused by enteric bacterial overgrowth and/or increased intestinal permeability to endotoxin. In this study, the effect of ethanol and acetaldehyde on the paracellular permeability was evaluated in Caco-2 cell monolayers. Ethanol was administered into the incubation medium, whereas acetaldehyde was administered by exposing cell monolayers to vapor phase acetaldehyde, or by direct administration of an acetaldehyde generating system (AGS), ethanol + NAD+ + alcohol dehydrogenase. Paracellular permeability was assessed by measuring transepithelial electrical resistance (TER), sodium chloride dilution potential, and unidirectional flux of D-[2-3H]mannitol. Administration of ethanol up to 900 mM produced no significant effect on paracellular permeability. Vapor phase acetaldehyde, generated from 5 to 167 mM acetaldehyde solutions in neighboring wells, resulted in a time- and dose- dependent increase in acetaldehyde concentration (99 to 760 μM) in the buffer bathing cell monolayer. Acetaldehyde induced a reduction of TER and dilution potential, and an elevation of mannitol flux in a time and concentration-related manner, without affecting the ability of cells to exclude trypan blue. Removal of acetaldehyde after 1, 2, or 4 hr treatment and subsequent incubation in the absence of acetaldehyde resulted in a time- dependent reversal of TER to baseline values. Administration of AGS also reduced TER and dilution potential, associated with an increase in mannitol flux. This effect of AGS was prevented by 4-methylpyrazole, an alcohol dehydrogenase inhibitor. These results show that acetaldehyde, but not ethanol, reversibly increases the paracellular permeability of Caco-2 cell monolayer.

UR - http://www.scopus.com/inward/record.url?scp=0031761303&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031761303&partnerID=8YFLogxK

U2 - 10.1111/j.1530-0277.1998.tb03972.x

DO - 10.1111/j.1530-0277.1998.tb03972.x

M3 - Article

VL - 22

SP - 1724

EP - 1730

JO - Alcoholism: Clinical and Experimental Research

JF - Alcoholism: Clinical and Experimental Research

SN - 0145-6008

IS - 8

ER -